The goal of this project is to identify the mechanisms and sites of action of analgesic drugs. Using the technique of microiontophoresis, I will try to identify the neurotransmitters(s) in the nociceptive pathway of the mesencephalic reticular formation (MRF). The technique of microiontophoresis will also be used to determine the mechanism of action (e.g. interactions with cyclic nucleotides) of morphine and other analgesic drugs in the MRF. A second technique that will be used is to record single unit activity in freely moving rats and to correlate changes in neuronal firing related to nociception. Therefore, systemic administration of narcotic analgesic drugs should abolish both the neuronal firing pattern and behavioral response evoked by a nociceptive stimulus. The neuronal patterns associated with nociception will be analyzed using computer techniques. Perhaps using this technique we may be able to understand the information coding process in the brain so that in the future subtle changes in firing pattern can be appreciated and interpreted. A third technique that will be used is to microinject morphine into the MRF and determine if cAMP will antagonize the analgesic effects of morphine; we have shown that cAMP antagonizes the ability of morphine and met-enkephalin to block the increase in neuronal firing evoked by a nociceptive stimulus. Using this technique we will also test the effects of drugs that decrease the endogenous levels of cAMP to determine if this pharmocologic manipulation will produce analgesia alone or enhance the analgesic effects of morphine. These proposed experiments will allow a better understanding of both the mechanism and sites of action of analgesic drugs. Furthermore they will further our understanding of brain function. If both of these goals are achieved it may be possible to produce analgesia without using narcotic or addicting drugs.